Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dendritic cells (DCs) are antigen presenting cells which serve as a passage between the innate and the acquired immunity. Aspergillosis is a major lethal condition in immunocompromised patients caused by the adaptable saprophytic fungus Aspergillus fumigatus. The healthy human immune system is capable to ward off A. fumigatus infections however immune-deficient patients are highly vulnerable to invasive aspergillosis. A. fumigatus can persist during infection due to its ability to survive the immune response of human DCs. Therefore, the study of the metabolism specific to the context of infection may allow us to gain insight into the adaptation strategies of both the pathogen and the immune cells. We established a metabolic model of A. fumigatus central metabolism during infection of DCs and calculated the metabolic pathway (elementary modes; EMs). Transcriptome data were used to identify pathways activated when A. fumigatus is challenged with DCs. In particular, amino acid metabolic pathways, alternative carbon metabolic pathways and stress regulating enzymes were found to be active. Metabolic flux modeling identified further active enzymes such as alcohol dehydrogenase, inositol oxygenase and GTP cyclohydrolase participating in different stress responses in A. fumigatus. These were further validated by qRT-PCR from RNA extracted under these different conditions. For DCs, we outlined the activation of metabolic pathways in response to the confrontation with A. fumigatus. We found the fatty acid metabolism plays a crucial role, along with other metabolic changes. The gene expression data and their analysis illuminate additional regulatory pathways activated in the DCs apart from interleukin regulation. In particular, Toll-like receptor signaling, NOD-like receptor signaling and RIG-I-like receptor signaling were active pathways. Moreover, we identified subnetworks and several novel key regulators such as UBC, EGFR, and CUL3 of DCs to be activated in response to A. fumigatus. In conclusion, we analyze the metabolic and regulatory responses of A. fumigatus and DCs when confronted with each other.
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PMID:Aspergillus fumigatus Challenged by Human Dendritic Cells: Metabolic and Regulatory Pathway Responses Testify a Tight Battle. 3119 61

The aim of this paper was to explore the pharmacological mechanism of Baitouweng Decoction in the treatment of ulcerative colitis(UC) by network pharmacology and to preliminarily verify the related targets by animal experiments. Cytoscape software was used to construct "ingredient-target-disease" network through TCMSP, GeneCards and Uniprot databases. The protein interaction network was constructed using STRING database, and the core targets were speculated. The GO and KEGG enrichment analysis was conducted using R software. Autodock Vina software was used for molecular docking of ingredients and core targets. UC mice induced by dextran sodium sulfate(DSS) were treated by Baitouweng Decoction. The pathological changes of colon tissues were observed by HE staining, and the expression levels of related genes were analyzed by immunohistochemistry.The results showed that 26 active ingre-dients and 30 core targets were found in Baitouweng Decoction through network pharmacology. GO enrichment analysis showed that these genes mainly affected nuclear receptor activity, transcription factor activity, steroid hormone receptor activity, ubiquitin-like protein ligase binding, protein heterodimerization activity, transcription cofactor binding and other biological processes. KEGG enrichment analysis showed that P53 signaling pathway, EGFR signaling pathway, TNF signaling pathway, PI3 K-AKT signaling pathway and some cancer-related pathways were enriched. Molecular docking showed that EGFR, PPARG, CASP3, NOS3, caspase-9, CCND1, ADH, IL6 and NFKB1 were better docked with active ingredients. The experiments verified that Baitouweng Decoction could improve the colon pathology of mice, and EGFR is one of the related targets. Our study suggested that Baitouweng Decoction could treat UC through multiple targets and pathways, which provided a theoretical basis for future research.
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PMID:[Network pharmacological analysis and preliminary validation of mechanisms of Baitouweng Decoction in treatment of ulcerative colitis]. 3248 64